Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus
Year: 2018
Type: review
Study design: Observational Study
Abstract: Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (PAgP-Ger < 0.05; PCAD < 5 × 10−8; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02–1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05–1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
Source: Scientific Reports
Authors: Matthias Munz, Gesa M. Richter, Bruno G. Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Loreto Munoz, Anita Bhandari, Stephanie Tennstedt, Ingmar Staufenbiel, Nathalie van der Velde, André G. Uitterlinden, Lisette C. P. G. M. de Groot, Jürgen Wellmann, Klaus Berger, Bastian Krone, Per Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Henrik Dommisch, Jeanette Erdmann, Arne S. Schaefer
Institutions: Humboldt-Universität zu Berlin, Charité – Universitätsmedizin Berlin, University of Lübeck, Academic Center for Dentistry Amsterdam, Vrije Universiteit Amsterdam, University of Amsterdam, University of Bonn, University of North Carolina at Chapel Hill, Universitätsmedizin Greifswald, Universität Greifswald, Universitätszahnklinik Wien, Medical University of Vienna, University of Würzburg, Universitätsklinikum Würzburg, University Hospital Schleswig-Holstein, German Centre for Cardiovascular Research, Medizinische Hochschule Hannover, Erasmus MC, Amsterdam University Medical Centers, Wageningen University & Research, University of Münster, Institut für Medizinische Informatik, Biometrie und Epidemiologie, University Hospital of Basel, Christian-Albrechts-Universität zu Kiel, Berlin Institute of Health at Charité - Universitätsmedizin Berlin
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,757
Funders: Pfizer, European Commission, Deutsche Forschungsgemeinschaft, Fondation Leducq, Bundesministerium für Bildung und Forschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, Exzellenzclusters Entzündungsforschung, Deutsche Migräne- und Kopfschmerzgesellschaft e.V., Heinz Nixdorf Stiftung, Universität Greifswald, Ministry of Cultural Affairs, Cilag
Awards: Understanding coronary artery disease genes, G1518085888, G1916810480, G2207173938, Verbundprojekt: Spitzenforschung und Innovation in den Neuen Ländern - GANI_MED - Greifswald Approach to Individualized Medicine, Verbundprojekt: Nationales Genomforschungsnetz 2: Systematisch-Methodische Plattform GEM: Standort Kiel: PopGen: Populationsrepräsentative Biobank Schleswig-Holstein, G2396948287, G2950734072, G3041445225, G3283323707, AgroClustEr: FoCus - Food Chain Plus. Verbund Gesundheitliche Bewertung und Konsumentenverhalten., G3868930229, G3896511197, Sharing capacity across Europe in high-throughput sequencing technology to explore genetic variation in health and disease, Die bidirektionale Analyse der Beziehung zwischen subklinischer Arteriosklerose und der Depression (BiDirect), Anwendung von DNA-Array-Technologien in Molekularer Medizin und Mikrobiologie, G4764896896, G49395674, Verbesserung der Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, Phase II, G512922464, G5233356934, G5367459596, G6029994567, G6413504379, G7086254578, G7453583093, G7660237446, G8399513454, Verbesserung der Struktur- und Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, G915808470, Zentrale Biomaterialbank der Universität Kiel: Das popgen 2.0-Netzwerk
OpenAlex ID: W2891557666